RESUMO
UNLABELLED: Fludarabine-based regimens are highly effective as first-line therapy in patients with follicular lymphoma. Nevertheless, noticeable haematological toxicity has been reported using fludarabine-based regimens. AIM: To analyse the combination of low-dose oral fludarabine and cyclophosphamide plus rituximab (FCR) as induction therapy, followed by rituximab as maintenance therapy. METHODS: We retrospectively analysed 73 patients diagnosed with low-grade follicular lymphoma treated with two different schemes: attenuated oral (AO) and standard intravenous (SIV) FCR. RESULTS: Overall response rate (ORR) was 95% (complete response rate, CRR 79.5%, partial response, PR 15.4%). CRR was 84.6% in AO vs. 61.9% in SIV (P = 0.058). 44.4% of patients underwent maintenance therapy. Grade 3-4 toxicities included neutropenia: 65.4%; anaemia: 39.7%; thrombocytopenia: five patients; infectious complications: six patients. There were no treatment-related deaths. 6.8% had a secondary malignancy. Progression-free survival (PFS) was 84.6% at 12 yr. The following variables influenced PFS in multivariate analysis: Hb < 12 g/dL [HR 4.7 (95% CI 1.18-18.6)], response after induction [HR 4.9 (95% CI 1.01-24)] for PR vs. CR and [HR 21.27 (95% CI 4.33-104)] for SD/DP vs. CR. OS was 83.1% at 12 yr. The following variables significantly influenced OS in multivariate analysis: not receiving rituximab as maintenance therapy (HR 10.7 (95% CI 1.4-82.5), increased levels of ß2-microglobulin [HR 5.2 (95% CI 1.16-23.7)]. CONCLUSIONS: FCR allowed us to obtain a high response rate, which translated into promising progression free and overall survival with an acceptable and manageable toxicity profile, especially with the attenuated oral scheme.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidade , Masculino , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Rituximab , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
Pharmacogenetics correlates certain genetic variants, such as single nucleotide polymorphisms (SNPs), with blood drug levels, efficacy, and adverse effects of the treatment. Tacrolimus is mainly metabolized via CYP3A4/5, whereas CYP2C19 and CYP3A4/5 are responsible for omeprazole metabolism. Omeprazole inhibits tacrolimus metabolism via CYP3A5 in patients carrying variant alleles of CYP2C19, increasing tacrolimus blood concentrations. Seventy-five renal transplant recipients treated with tacrolimus and concomitant omeprazole were genotyped in a panel of 37 SNPs with use of Sequenom MassArray. The patients with CYP2C19*2/*2 genotype (n = 4) showed a median posttransplantation hospital stay of 27.5 days (95% confidence interval [CI], 23-39 days), compared with 12 days (95% CI, 10-15 days) in patients with CYP2C19*1/*1 or CYP2C19*1/*2 (n = 71; P = 0.016, Kruskal-Wallis test).The difference in hospital stay was directly correlated with an increase in tacrolimus levels (C(min)/[dose/weight]) during the first week after trasplantation (in 59 patients with data on levels; P = 0.021, Kruskal-Wallis), excluding the patients with atypical metabolisms due to CYP3A5*1/*3 or CYP3A5*1/*1 genotype. Recipients with CYP2C19*2/*2 genotype also showed allograft delayed function (acute tubular necrosis in 3 patients). Genotyping of CYP3A5 and CYP2C19 in renal transplantation should be considered to be of interest when treating with tacrolimus and omeprazole, because CYP2C19*2/*2 variant indirectly elicits an increase of tacrolimus blood levels and, in our study population, the adverse effects described.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Imunossupressores/farmacocinética , Transplante de Rim/imunologia , Tempo de Internação , Omeprazol/farmacocinética , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/genética , Inibidores da Bomba de Prótons/farmacocinética , Tacrolimo/farmacocinética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Distribuição de Qui-Quadrado , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A , Interações Medicamentosas , Monitoramento de Medicamentos , Indução Enzimática , Inibidores Enzimáticos/farmacocinética , Feminino , Predisposição Genética para Doença , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Masculino , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Omeprazol/efeitos adversos , Farmacogenética , Fenótipo , Complicações Pós-Operatórias/etiologia , Inibidores da Bomba de Prótons/efeitos adversos , Especificidade por Substrato , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/sangueAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Micose Fungoide/tratamento farmacológico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bexaroteno , Ciclofosfamida/administração & dosagem , Humanos , Pentostatina/administração & dosagem , Tetra-Hidronaftalenos/administração & dosagem , Resultado do TratamentoRESUMO
Microglial cells are one of the interstitial elements of the pineal gland (PG). We recently reported the pattern of microglia colonization and activation, and microglia-Pax6+ cell interactions during normal pineal ontogeny. Here, we describe the dynamics of microglia-Pax6+ cell associations and interactions after surgical or pharmacological manipulation. In adult rats, the superior cervical ganglia (SCG) were exposed, and either bilaterally excised (SCGx) or decentralized (SCGd). In the SCGx PGs, the density of Iba1+ microglia increased after surgery and returned to sham baseline levels 13 days later. Pineal microglia also responded to SCGd, a more subtle denervation. The number of clustered Iba1+ /PCNA+ /ED1+ microglia was higher 4 days after both surgeries compared to the sham-operated group. However, the number of Pax6+ /PCNA- cells and the percentage of Pax6+ cells contacted by and/or phagocytosed by microglia increased significantly only after SCGx. Separate groups of rats were treated with either bacterial lipopolysaccharides (LPS) or doxycycline (DOX) to activate or inhibit pineal microglia, respectively. Peripheral LPS administration caused an increase in the number of clustered Iba1+ /PCNA+ /ED1+ microglial cells, and in the percentage of Pax6+ cells associated with and/or engulfed by microglia. In the LPS-treated PGs, we also noted an increase in the number of PCNA+ cells that were Iba1- within the microglial cell clusters. The density of Pax6+ cells did not change after LPS treatment. DOX administration did not influence the parameters analyzed. These data suggest that pineal microglia are highly receptive cells capable of rapidly responding in a differential manner to surgical and pharmacological stimuli.
Assuntos
Microglia/fisiologia , Estimulação Física , Glândula Pineal/efeitos dos fármacos , Glândula Pineal/cirurgia , Animais , Antibacterianos/farmacologia , Proteínas de Ligação ao Cálcio/metabolismo , Doxiciclina/farmacologia , Gânglios Espinais/cirurgia , Lipopolissacarídeos/farmacologia , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Neurocirurgia , Fator de Transcrição PAX6 , Fagocitose , Glândula Pineal/citologia , Ratos , Ratos WistarRESUMO
Thoracic trauma is a challenging situation with potential severe chest wall and intrathoracic organ injuries. We present a case of emergent surgery in a 23-year-old man with hemorrhagic shock due to massive lung and chest wall injury after thoracic trauma in a water slide. We performed a SI-VATS approach in order to define intrathoracic and chest wall injuries, and once checked the extension of the chest wall injury, we added a middle size thoracotomy just over the affected area in order to stabilize rib fractures with Judet plates, that had caused massive laceration in left lower lobe (LLL) and injured the pericardium causing myocardical tear. After checking bronchial and vascular viability of LLL we suggested a lung parenchyma preserving technique with PTFE protected pulmonary primary suture in order to avoid a lobectomy. Chest tubes were removed on 3rd postoperative day and patient was discharged on 14th postoperative day. He has already recovered his normal activity 6 months after surgery.
RESUMO
Mammalian circadian rhythms are controlled by a master pacemaker located in the suprachiasmatic nuclei (SCN), which is synchronized to the environment by photic and nonphotic stimuli. One of the main functions of the SCN is to regulate peripheral oscillators to set temporal variations in the homeostatic control of physiology and metabolism. In this sense, the SCN coordinate the activity/rest and feeding/fasting rhythms setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism. One of the major time cues to the periphery is the nocturnal melatonin, which is synthesized and secreted by the pineal gland. Under SCN control, arylalkylamine N-acetyltransferase (AA-NAT)-the main enzyme regulating melatonin synthesis in vertebrates-is activated at night by sympathetic innervation that includes the superior cervical ganglia (SCG). Bilateral surgical removal of the superior cervical ganglia (SCGx) is considered a reliable procedure to completely prevent the nocturnal AA-NAT activation, irreversibly suppressing melatonin rhythmicity. In the present work, we studied the effects of SCGx on rat metabolic parameters and diurnal rhythms of feeding and locomotor activity. We found a significant difference between SCGx and sham-operated rats in metabolic variables such as an increased body weight/food intake ratio, increased adipose tissue, and decreased glycemia with a normal glucose tolerance. An analysis of locomotor activity and feeding rhythms showed an increased daytime (lights on) activity (including food consumption) in the SCGx group. These alterations suggest that superior cervical ganglia-related feedback mechanisms play a role in SCN-periphery phase coordination and that SCGx is a valid model without brain-invasive surgery to explore how sympathetic innervation affects daily (24 h) patterns of activity, food consumption and, ultimately, its role in metabolism homeostasis.
RESUMO
Worldwide accepted indications of anatomical segmentectomies are mainly early stage primary adenocarcinomas, pulmonary metastasis and benign conditions. Their performance through uniportal VATS has become more and more popular due to the less invasiveness of the whole procedure under this approach. Recently, many efforts have focused on non-intubated spontaneously breathing management of lobectomies and anatomical segmentectomies, although specific selection criteria and main advantages are not completely standardized. In a 62-year-old thin man with two pulmonary residual metastasis from sigma adenocarcinoma, after chemotherapy plus antiangiogenic treatment, we indicated a single-incision video-assisted left-lower lobe (LLL) upper segmentectomy (S6) under spontaneous breathing and intercostal blockade. Total operation time was 240 minutes. Chest tube was removed at 24 hours and the patient was discharge on postoperative day 2 without any complication. Non-intubated uniportal VATS is a safe and reasonable approach for lung-sparing resections in selected patients, although more evidence is required for selecting which patients can benefit more over standard intubated procedures.
RESUMO
Endobronchial lipomas are rare benign tumors whose symptoms are usually confused with recurrent infections or even asthma diagnosis, and mostly caused by endobronquial obstructive component which also conditions severity. We report a case of a 60-year-old man with a right-lower lobe upper-segment endobronchial myxoid tumor with uncertain diagnosis. We performed a single incision video-assisted anatomical segmentectomy and wedge bronchoplasty with handsewn closure to achieve complete resection and definitive diagnosis. During the postoperative air leak was not observed and there was no complication, with low pain scores and complete recovery. Final pathological exam showed endobronchial lipoma. Single-incision (SI) anatomical segmentectomies are lung-sparing resections for benign or low-grade malignancies with diagnostic and therapeutic value, and the need for a wedge bronchoplasty is not a necessary indication for conversion to multiport or open thoracotomy.